2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to be one of the most toxic small molecules known and has caused toxic effects and death in experimental animals at parts per trillion levels. The extreme toxicity as well as the diverse effects observed from TCDD intoxication have complicated efforts to determine the mechanisms by which TXDD toxicity are manifested. The proposed research is designed to help elucidate these mechanisms. We have shown that TCDD, unlike most chlorinated hydrocarbons, is not metabolized to any measureable extent by liver microsomal enzymes in vitro. The emphasis of the proposed research will be to evaluate toxic effects on cells focusing mainly on the use of cell culture for this purpose. General toxicity, membrane effects, transformation and promotion of other transformants are projected using a viaiety of cell types. These effects will be compared to similar alterations in in vivo systems. To date is has not been possible to administer TCDD to cells in culture due to the insoluble nature of TCDD in aqueous systems. Through the use of lipid carriers, we propose to overcome this problem and conduct the aforememtioned projects.